| IED ID | IndEnz0005000462 |
| Enzyme Type ID | lipase000462 |
| Protein Name |
Angiopoietin-related protein 4 Angiopoietin-like protein 4 Hepatic fibrinogen/angiopoietin-related protein HFARP Cleaved into: ANGPTL4 N-terminal chain; ANGPTL4 C-terminal chain |
| Gene Name | ANGPTL4 ARP4 HFARP PGAR PP1158 PSEC0166 UNQ171/PRO197 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSGAPTAGAALMLCAATAVLLSAQGGPVQSKSPRFASWDEMNVLAHGLLQLGQGLREHAERTRSQLSALERRLSACGSACQGTEGSTDLPLAPESRVDPEVLHSLQTQLKAQNSRIQQLFHKVAQQQRHLEKQHLRIQHLQSQFGLLDHKHLDHEVAKPARRKRLPEMAQPVDPAHNVSRLHRLPRDCQELFQVGERQSGLFEIQPQGSPPFLVNCKMTSDGGWTVIQRRHDGSVDFNRPWEAYKAGFGDPHGEFWLGLEKVHSITGDRNSRLAVQLRDWDGNAELLQFSVHLGGEDTAYSLQLTAPVAGQLGATTVPPSGLSVPFSTWDQDHDLRRDKNCAKSLSGGWWFGTCSHSNLNGQYFRSIPQQRQKLKKGIFWKTWRGRYYPLQATTMLIQPMAAEAAS |
| Enzyme Length | 406 |
| Uniprot Accession Number | Q9BY76 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697, PubMed:27929370, PubMed:29899144). May also play a role in regulating glucose homeostasis and insulin sensitivity (Probable). Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage (PubMed:14583458, PubMed:17068295). Upon heterologous expression, inhibits the adhesion of endothelial cell to the extracellular matrix (ECM), and inhibits the reorganization of the actin cytoskeleton, formation of actin stress fibers and focal adhesions in endothelial cells that have adhered to ANGPTL4-containing ECM (in vitro) (PubMed:17068295). Depending on context, may modulate tumor-related angiogenesis (By similarity). {ECO:0000250|UniProtKB:Q9Z1P8, ECO:0000269|PubMed:14583458, ECO:0000269|PubMed:17068295, ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:21398697, ECO:0000269|PubMed:27929370, ECO:0000269|PubMed:29899144, ECO:0000305|PubMed:29899519}.; FUNCTION: [ANGPTL4 N-terminal chain]: Mediates inactivation of the lipoprotein lipase LPL, and thereby plays an important role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697, PubMed:27929370, PubMed:29899144). Has higher activity in LPL inactivation than the uncleaved protein (PubMed:19270337, PubMed:21398697). {ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:21398697, ECO:0000269|PubMed:27929370, ECO:0000269|PubMed:29899144}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Beta strand (10); Chain (3); Coiled coil (1); Disulfide bond (2); Domain (1); Erroneous initiation (1); Glycosylation (1); Helix (8); Mutagenesis (8); Natural variant (28); Sequence conflict (11); Signal peptide (1); Site (1) |
| Keywords | 3D-structure;Alternative splicing;Angiogenesis;Coiled coil;Direct protein sequencing;Disulfide bond;Extracellular matrix;Glycoprotein;Lipid metabolism;Reference proteome;Secreted;Signal |
| Interact With | Itself; P05556; P18084 |
| Induction | INDUCTION: Up-regulated when cells are exposed to severe hypoxia (in vitro). {ECO:0000269|PubMed:17068295}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10698685, ECO:0000269|PubMed:14583458, ECO:0000269|PubMed:17068295, ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:21398697, ECO:0000269|PubMed:29899519}. Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:17068295, ECO:0000269|PubMed:21398697}. Note=The unprocessed form interacts with the extracellular matrix (PubMed:17068295, PubMed:21398697). This may constitute a dynamic reservoir, a regulatory mechanism of the bioavailability of ANGPTL4 (Probable). {ECO:0000269|PubMed:17068295, ECO:0000269|PubMed:21398697, ECO:0000305|PubMed:17068295}. |
| Modified Residue | |
| Post Translational Modification | PTM: N-glycosylated. {ECO:0000269|PubMed:10698685}.; PTM: [ANGPTL4 N-terminal chain]: Forms disulfide-linked dimers and tetramers. {ECO:0000269|PubMed:19270337}.; PTM: Cleaved into a smaller N-terminal chain and a larger chain that contains the fibrinogen C-terminal domain; both cleaved and uncleaved forms are detected in the extracellular space. The cleaved form is not present within the cell. {ECO:0000269|PubMed:17068295, ECO:0000269|PubMed:19270337, ECO:0000269|PubMed:21398697}. |
| Signal Peptide | SIGNAL 1..25; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (4) |
| Cross Reference PDB | 6EUB; 6U0A; 6U1U; 6U73; |
| Mapped Pubmed ID | 10900462; 16109723; 17088546; 19028676; 19060906; 19318355; 19710929; 19878569; 19934321; 20581395; 21397862; 22740495; 24397894; 25640309; 26933753; 26934567; 26934667; 8020465; |
| Motif | |
| Gene Encoded By | |
| Mass | 45,214 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |